A Phase II, Double-Blind, Randomized, Placebo-Controlled, Multicenter Trial to Assess the Safety and Efficacy of 5% Monolaurin Vaginal Gel Administered Intravaginally for the Treatment of Bacterial Vaginosis DMID Protocol Number: 12-0021 DMID Funding Mechanism: VTEU Contract Support Pharmaceutical Support Provided by: Hennepin Life Sciences Other Identifying Numbers: None IND Sponsor: Division of Microbiology and Infectious Diseases The National Institute of Allergy and Infectious Diseases The National Institutes of Health Principal Investigator: Patricia Winokur, MD DMID Clinical Project Manager: Barbara Hahn, RN, BSN DMID Medical Monitor: Soju Chang, MD Version 8 23 May 2017 1 DMID Protocol No. 12-0021 Version 8.0 23May2017 STATEMENT OF COMPLIANCE This trial will be conducted in compliance with the protocol, International Conference on Harmonisation guideline E6: Good Clinical Practice: Consolidated Guideline, the applicable regulatory requirements from US Code of Federal Regulations (CFR) (Title 45 CFR Part 46 and Title 21 CFR including Parts 50 and 56) concerning informed consent and Institutional Review Board regulations, and the NIAID Clinical Terms of Award. All individuals responsible for the design and conduct of this study have completed Human Subjects Protection Training and are qualified to be conducting this research prior to the enrollment of any subjects. Curricula vitae for all investigators and sub-investigators participating in this trial are on file in a central facility (21 CFR 312.23 [a] [6] [iii] [b] edition). 2 DMID Protocol No. 12-0021 Version 8.0 23May2017 SIGNATURE PAGE The signature below constitutes the approval of this protocol and the attachments, and provides the necessary assurances that this trial will be conducted according to all stipulations of the protocol, including all statements regarding confidentiality, and according to local legal and regulatory requirements and applicable US federal regulations and ICH guidelines. Site Investigator: Signed: Date: Name Title 3 DMID Protocol No. 12-0021 Version 8.0 23May2017 TABLE OF CONTENTS STATEMENT OF COMPLIANCE ............................................................................................. 2 SIGNATURE PAGE................................................................................................................... 3 TABLE OF CONTENTS ............................................................................................................ 4 LIST OF TABLES ...................................................................................................................... 7 LIST OF FIGURES .................................................................................................................... 8 LIST OF ABBREVIATIONS ..................................................................................................... 9 PROTOCOL SUMMARY ........................................................................................................ 12 1. KEY ROLES .......................................................................................................... 15 2. BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE ................... 17 2.1. Background Information ......................................................................................... 17 2.1.1. Monolaurin (GML) ................................................................................................. 19 2.2. Rationale ................................................................................................................ 23 2.3. Potential Risks and Benefits.................................................................................... 23 2.3.1. Potential Risks ........................................................................................................ 23 2.3.2. Known Potential Benefits ....................................................................................... 24 3. OBJECTIVES ........................................................................................................ 25 3.1. Study Objectives ..................................................................................................... 25 3.2. Study Outcome Measures ....................................................................................... 25 3.2.1. Safety Outcomes ..................................................................................................... 25 3.2.2. Efficacy Outcomes.................................................................................................. 26 3.2.2.1. Primary and Secondary Efficacy Outcomes ............................................................ 26 3.2.2.2. Exploratory Efficacy Outcomes .............................................................................. 26 4. STUDY DESIGN ................................................................................................... 27 4.1. Substudies (if applicable) ........................................................................................ 28 5. STUDY ENROLLMENT AND WITHDRAWAL ................................................... 29 5.1. Subject Inclusion Criteria ....................................................................................... 29 5.2. Subject Exclusion Criteria ....................................................................................... 29 5.3. Treatment Assignment Procedures .......................................................................... 31 5.3.1. Randomization Procedures ..................................................................................... 31 5.3.2. Masking Procedures ............................................................................................... 31 5.3.3. Reasons for Withdrawal.......................................................................................... 32 5.3.4. Handling of Withdrawals ........................................................................................ 32 4 DMID Protocol No. 12-0021 Version 8.0 23May2017 5.3.5. Termination of Study .............................................................................................. 33 6. STUDY INTERVENTION/INVESTIGATIONAL PRODUCT ............................... 34 6.1. Study Product Description ...................................................................................... 34 6.1.1. Acquisition ............................................................................................................. 34 6.1.2. Formulation, Packaging, and Labeling .................................................................... 34 6.1.2.1. 5% Monolaurin Vaginal Gel ................................................................................... 35 6.1.2.2. Vehicle Placebo Gel ............................................................................................... 35 6.1.3. Product Storage and Stability .................................................................................. 35 6.2. Dosage, Preparation and Administration of Study Intervention/Investigational Product ................................................................................................................... 35 6.3. Modification of Study Intervention/Investigational Product for a Participant .......... 36 6.4. Accountability Procedures for the Study Intervention/Investigational Product(s) ............................................................................................................... 36 6.5. Assessment of Subject Compliance with Study Intervention/Investigational Product ................................................................................................................... 36 6.6. Concomitant Medications/Treatments ..................................................................... 37 7. STUDY SCHEDULE .............................................................................................. 38 7.1. Screening and Enrollment (Visit 1, Day 1) .............................................................. 38 7.2. Visit 2 (Day 8 [Window: Days 8-15]) ..................................................................... 41 7.3. Visit 3, Final Study Visit (Day 28 [Window: Days 22-31]) ...................................... 42 7.4. Early Termination Visit .......................................................................................... 43 7.5. Unscheduled Visit .................................................................................................. 43 8. STUDY PROCEDURES/EVALUATIONS ............................................................. 45 8.1. Clinical Evaluations ................................................................................................ 45 8.2. Laboratory Evaluations ........................................................................................... 45 8.2.1. Clinical Laboratory Evaluations .............................................................................. 45 8.2.2. Special Assays or Procedures .................................................................................. 46 8.2.3. Specimen Preparation, Handling, and Shipping....................................................... 47 8.2.3.1. Instructions for Specimen Preparation, Handling, and Storage ................................ 47 8.2.3.2. Specimen Shipment ................................................................................................ 47 9. ASSESSMENT OF SAFETY .................................................................................. 49 9.1. Specification of Safety Parameters .........................................................................